Venous thromboembolism and bleeding in critically ill patients with severe renal insufficiency receiving dalteparin thromboprophylaxis: prevalence, incidence and risk factors

Deborah Cook, James Douketis, Maureen Meade, Gordon Guyatt, Nicole Zytaruk, John Granton, Yoanna Skrobik, Martin Albert, Robert Fowler, Paul Hebert, Guiseppe Pagliarello, Jan Friedrich, Andreas Freitag, Tim Karachi, Christian Rabbat, Diane Heels-Ansdell, William Geerts, Mark Crowther, Canadian Critical Care Trials Group, Ellen McDonald, France Clarke, Andrea Tkaczyk, Deborah Cook, Karen Woods, Maureen Meade, Christine Wynne, Mark Duffett, Andreas Freitag, Marilyn Steinberg, Andrea Matte, John Granton, France Clarke, Andrea Tkaczyk, Tim Karachi, Mary-Jo Lewis, Julia Foxall, Guiseppe Pagliarello, Irene Watpool, Tracy McArdle, Paul Hebert, Johanne Harvey, Yoanna Skrobik, Carole Sirois, Carole Nadon, Martin Albert, Mel Keogh, Craig Dale, Rob Fowler, Orla Smith, Andrea Richards, Ines DeCampos, Jan Friedrich, John Marshall, James Douketis, Deborah Cook, Mark Crowther, Maureen Meade, Gordon Guyatt, David Anderson, William Geerts, Nicole Zytaruk, Diane Heels-Ansdell, Lehana Thabane, Lori Linkins, Darin Treleaven, Tasnim Sinuff, Rakesh Patel, Christian Rabbat, Agnes Lee, Martin O'Donnell, Deborah Cook, James Douketis, Maureen Meade, Gordon Guyatt, Nicole Zytaruk, John Granton, Yoanna Skrobik, Martin Albert, Robert Fowler, Paul Hebert, Guiseppe Pagliarello, Jan Friedrich, Andreas Freitag, Tim Karachi, Christian Rabbat, Diane Heels-Ansdell, William Geerts, Mark Crowther, Canadian Critical Care Trials Group, Ellen McDonald, France Clarke, Andrea Tkaczyk, Deborah Cook, Karen Woods, Maureen Meade, Christine Wynne, Mark Duffett, Andreas Freitag, Marilyn Steinberg, Andrea Matte, John Granton, France Clarke, Andrea Tkaczyk, Tim Karachi, Mary-Jo Lewis, Julia Foxall, Guiseppe Pagliarello, Irene Watpool, Tracy McArdle, Paul Hebert, Johanne Harvey, Yoanna Skrobik, Carole Sirois, Carole Nadon, Martin Albert, Mel Keogh, Craig Dale, Rob Fowler, Orla Smith, Andrea Richards, Ines DeCampos, Jan Friedrich, John Marshall, James Douketis, Deborah Cook, Mark Crowther, Maureen Meade, Gordon Guyatt, David Anderson, William Geerts, Nicole Zytaruk, Diane Heels-Ansdell, Lehana Thabane, Lori Linkins, Darin Treleaven, Tasnim Sinuff, Rakesh Patel, Christian Rabbat, Agnes Lee, Martin O'Donnell

Abstract

Background: Critically ill patients with renal insufficiency are predisposed to both deep vein thrombosis (DVT) and bleeding. The objective of the present study was to evaluate the prevalence, incidence and predictors of DVT and the incidence of bleeding in intensive care unit (ICU) patients with estimated creatinine clearance <30 ml/min.

Methods: In a multicenter, open-label, prospective cohort study of critically ill patients with severe acute or chronic renal insufficiency or dialysis receiving subcutaneous dalteparin 5,000 IU once daily, we estimated the prevalence of proximal DVT by screening compression venous ultrasound of the lower limbs within 48 hours of ICU admission. DVT incidence was assessed on twice-weekly ultrasound testing. We estimated the incidence of major and minor bleeding by daily clinical assessments. We used Cox proportional hazards regression to identify independent predictors of both DVT and major bleeding.

Results: Of 156 patients with a mean (standard deviation) creatinine clearance of 18.9 (6.5) ml/min, 18 had DVT or pulmonary embolism within 48 hours of ICU admission, died or were discharged before ultrasound testing - leaving 138 evaluable patients who received at least one dose of dalteparin. The median duration of dalteparin administration was 7 days (interquartile range, 4 to 12 days). DVT developed in seven patients (5.1%; 95% confidence interval, 2.5 to 10.1). The only independent risk factor for DVT was an elevated baseline Acute Physiology and Chronic Health Evaluation II score (hazard ratio for 10-point increase, 2.25; 95% confidence interval, 1.03 to 4.91). Major bleeding developed in 10 patients (7.2%; 95% confidence interval, 4.0 to 12.8), all with trough anti-activated factor X levels </= 0.18 IU/ml. Independent risk factors for major bleeding were aspirin use (hazard ratio, 6.30; 95% confidence interval, 1.35 to 29.4) and a high International Normalized Ratio (hazard ratio for 0.5-unit increase, 1.68; 95% confidence interval, 1.07 to 2.66).

Conclusion: In ICU patients with renal insufficiency, the incidence of DVT and major bleeding are considerable but appear related to patient comorbidities rather than to an inadequate or excessive anticoagulant from thromboprophylaxis with dalteparin.

Trial registration: ClinicalTrials.gov NCT00138099.

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